High-definition spatial transcriptomics for in situ tissue profiling
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Summary
Tissue function relies on the precise spatial organization of cells characterized by distinct molecular profiles. Single-cell RNA-Seq captures molecular profiles but not spatial organization. Conversely, spatial profiling assays to date have lacked global transcriptome information, throughput or single-cell resolution. Here, we develop High-Density Spatial Transcriptomics (HDST), a method for RNA-Seq at high spatial resolution. Spatially barcoded reverse transcription oligonucleotides are coupled to beads that are randomly deposited into tightly packed individual microsized wells on a slide. The position of each bead is decoded with sequential hybridization using complementary oligonucleotides providing a unique bead-specific spatial address. We then capture, and spatially in situ barcode, RNA from the histological tissue sections placed on the HDST array. HDST recovers hundreds of thousands of transcript-coupled spatial barcodes per experiment at 2 μm resolution. We demonstrate HDST in the mouse brain, use it to resolve spatial expression patterns and cell types, and show how to combine it with histological stains to relate expression patterns to tissue architecture and anatomy. HDST opens the way to spatial analysis of tissues at high resolution.
Tissue function relies on the precise spatial organization of cells characterized by distinct molecular profiles. Single-cell RNA-Seq captures molecular profiles but not spatial organization. Conversely, spatial profiling assays to date have lacked global transcriptome information, throughput or single-cell resolution. Here, we develop High-Density Spatial Transcriptomics (HDST), a method for RNA-Seq at high spatial resolution. Spatially barcoded reverse transcription oligonucleotides are coupled to beads that are randomly deposited into tightly packed individual microsized wells on a slide. The position of each bead is decoded with sequential hybridization using complementary oligonucleotides providing a unique bead-specific spatial address. We then capture, and spatially in situ barcode, RNA from the histological tissue sections placed on the HDST array. HDST recovers hundreds of thousands of transcript-coupled spatial barcodes per experiment at 2 μm resolution. We demonstrate HDST in the mouse brain, use it to resolve spatial expression patterns and cell types, and show how to combine it with histological stains to relate expression patterns to tissue architecture and anatomy. HDST opens the way to spatial analysis of tissues at high resolution.
Overall design
Three sections of the main olfactory bulb from adult C57BL/6J mice
Three sections of the main olfactory bulb from adult C57BL/6J mice
Technology
HDST
HDST
Platform
Illumina NextSeq 500
Illumina NextSeq 500
Species
Mus musculus
Tissues
Brain
Brain
Development stage
12 weekS
12 weekS
Citation
Vickovic S, Eraslan G, Salmén F, Klughammer J et al. High-definition spatial transcriptomics for in situ tissue profiling. Nat Methods 2019 Oct;16(10):987-990.
Vickovic S, Eraslan G, Salmén F, Klughammer J et al. High-definition spatial transcriptomics for in situ tissue profiling. Nat Methods 2019 Oct;16(10):987-990.
Submission date: 2019-05-03Update date: 2019-09-20
Sample number: 3
Accessions
GEO Series Accessions:
GSE130682